A Novel Cancer Therapeutic Using Thrombospondin 1 in Dendritic Cells

doi:10.1038/mt.2013.236

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Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/28489

Title:	A Novel Cancer Therapeutic Using Thrombospondin 1 in Dendritic Cells
Authors:	Weng, Tzu-Yang Huang, Shih-Shien Yen, Meng-Chi Lin, Chi-Chen Chen, Yi-Ling Lin, Chiu-Mei Chen, Wei-Ching Wang, Chih-Yang Chang, Jang-Yang Lai, Ming-Derg
Contributors:	老人服務事業管理系
Keywords:	REGULATORY T-CELLS IN-VIVO INDOLEAMINE 2,3-DIOXYGENASE ENDOTHELIAL-CELLS TYPE-1 REPEATS SKIN DELIVERY DNA VACCINE TGF-BETA ANTIGEN INFLAMMATION
Date:	2014-02
Issue Date:	2015-05-06 21:18:08 (UTC+8)
Publisher:	Nature Publishing Group
Abstract:	Induction of thrombospondin 1 (TSP-1) is generally assumed to suppress tumor growth through inhibiting angiogenesis; however, it is less clear how TSP-1 in dendritic cells (DCs) influences tumor progression. We investigated tumor growth and immune mechanism by downregulation of TSP-1 in dendritic cells. Administration of TSP-1 small hairpin RNA (shRNA) through the skin produced anticancer therapeutic effects. Tumorinfiltrating CD4(+) and CD8(+) T cells were increased after the administration of TSP-1 shRNA. The expression of interleukin-12 and interferon-7 in the lymph nodes was enhanced by injection of TSP-1 shRNA. Lymphocytes from the mice injected with TSP-1 shRNA selectively killed the tumor cells, and the cytotoxicity of lymphocytes was abolished by depletion of CD8(+) T cells. Injection of CD11c(+) TSP-1 knockout (TSP-1-KO) bone marrow derived DCs (BMDCs) delayed tumor growth in tumorbearing mice. Similarly, antitumor activity induced by TSP-1-K0 BMDCs was abrogated by depletion of CD8(+) T cells. In contrast, the administration of shRNAs targeting TSP-2, another TSP family member, did not extend the survival of tumor-bearing mice. Finally, TSP-1 shRNA functioned as an innmunotherapeutic adjuvant to augment the therapeutic efficacy of Neu DNA vaccination. Collectively, the downregulation of TSP-1 in DCs produces an effective antitumor response that is opposite to the protumor effects by silencing of TSP-1 within tumor cells.
Relation:	Molecular therapy, v.22 n.2, pp.292-302
Appears in Collections:	[Dept. of Senior Service and Health Management] Periodical Articles

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